Human heart showing surrounding veins and arteries to represent cardiovascular disease as predicted by polygenic risk scores
Credit: LEONELLO CALVETTI/SCIENCE PHOTO LIBRARY

A link has been established between earlier menopause, higher risk of cardiovascular disease (CVD), and cognitive problems later in life, in a new study published in Neurology. These Canadian researchers looked at whether age at menopause, vascular risk, and history of hormone therapy (HT) containing estrogens together influence cognition over a three-year follow-up period in more than 8,000 women.

“We found that going through this hormonal change earlier in life while also having cardiovascular risk factors is linked to greater cognitive problems when compared to men of the same age,” said senior author Jennifer Rabin, PhD, of the University of Toronto.

As a person ages, blood vessels, including those in the brain, can be damaged by controllable cardiovascular risk factors such as high blood pressure, diabetes and smoking. These risk factors not only increase a person’s risk of cardiovascular disease, they increase the risk of dementia. In this study, earlier menopause was defined as occurring before age 49.

“While cardiovascular risk factors are known to increase a person’s risk for dementia, what is lesser known is why women have a greater risk for Alzheimer’s disease than men,” said Rabin. “We examined if the hormonal change of menopause, specifically the timing of menopause, may play a role in this increased risk.”

The study involved 8,360 female participants and 8,360 male participants matched for age who were enrolled in the Canadian Longitudinal Study on Aging. The women had an average age at menopause of 50. All participants had an average age of 65 at the start of the study and were followed for three years.

Researchers divided the women into three groups: those who experienced earlier menopause between ages 35 and 48; average menopause between ages 49 and 52; and later menopause between ages 53 and 65. Researchers also looked at whether the women had used hormone therapy containing estrogens.

Researchers reviewed six cardiovascular risk factors in all participants: high LDL cholesterol, diabetes, obesity, smoking, high blood pressure, and prescriptions for medications to lower blood pressure.

Participants were given a series of thinking and memory tests at the start and the end of the study and cognitive scores were calculated for each participant. Researchers then examined the associations of cardiovascular risk with cognitive scores in female participants in the three groups and compared them to those of male participants.

After adjusting for factors such as age and education, researchers found that female participants with both earlier menopause and higher cardiovascular risk had lower cognitive scores three years later. For each one standard deviation increase in cardiovascular risk score, female participants with earlier menopause showed a 0.044 standard deviation decrease in cognitive scores, compared to male participants in the same age group who showed a 0.035 standard deviation decrease in cognitive scores.

Researchers did not find a similar association for female participants with average or later menopause. Hormone therapy did not affect the results.

“Our study suggests that earlier menopause may worsen the effects of high cardiovascular risk on cognitive decline,” said Rabin. “Since our study followed participants for only three years, more research is needed over longer periods of time. Our findings highlight that age at menopause as well as cardiovascular risk should be considered when developing prevention strategies for cognitive decline.”

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